2026-06-14T00:31:43Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/272802026-02-28T01:16:03Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud
author
Orea, María J
author
Angulo, Javier C
author
González-Corpas, Ana
author
Echegaray, David
author
Marvá, Marcos
author
Lobo, María V T
author
Colás, Begoña
author
Ropero, Santiago
2026-02-27T09:00:12Z
2026-02-27T09:00:12Z
2023-01-02
Int J Mol Sci . 2023 Jan 2;24(1):803.
Int J Mol Sci
36614243
https://hdl.handle.net/20.500.12105/27280
Castration-resistant prostate cancer (CRPC) development is the foremost concern after treatment of patients with high risk with locally advanced or metastatic prostate cancer. Androgen receptor (AR) is the main driver of CRPC development, through its interaction with epigenetic modifier genes, placing epigenetics modifications in the forefront of CRPC development. Comparing the DNA methylation and expression profile of androgen-sensitive and -refractory prostate cancer cells, we describe the epigenetic silencing of claudin-3 (CLDN3) in AR positive cells resistant to androgen deprivation (LNCaP-abl). CLDN3 silencing was associated with DNA methylation, loss of histone acetylation and H3K27 methylation, and was re-expressed by the combined treatment with the epigenetic modulators Aza and SAHA. From a functional point of view, CLDN3 loss was associated with increased cellular invasion. Immunohistochemical analysis showed decreased CLDN3 expression in samples from CRPC patients. Interestingly, CLDN3 expression was significantly decreased in samples from patients with high total Gleason score (≥8) and locally advanced tumors. Finally, CLDN3 loss of expression was associated with worse disease-free survival and time to clinical progression. In conclusion, our findings strongly indicate that epigenetic silencing of CLDN3 is a common event in CRPC that could be useful as a molecular marker for the prognosis of prostate cancer patients and to discriminate aggressive from indolent prostate tumors.
eng
CLDN3
DNA methylation
castration-resistant prostate cancer
prognosis
prostate
Claudin-3 Loss of Expression Is a Prognostic Marker in Castration-Resistant Prostate Cancer.
research article
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URL
https://repisalud.isciii.es/bitstreams/f3459d79-985a-44aa-ba6e-db13d060d99f/download
File
MD5
99c7f29294756a875af4ab433468ae46
3810886
application/pdf
CLAUDIN3LOSS_2022.pdf